Anti-anxiety drugs in wastewater impact fish behavior

Benzodiazepines make fish bold, aggressive eaters.

Benzodiazepines are a highly effective group of pharmaceutical drugs that help millions of people cope with anxiety, insomnia, and panic disorders each year. These drugs work by binding to receptors in the brain and enhancing the effect of a neurotransmitter called GABA.

But humans aren’t the only animals with GABA and GABA receptors; several other species—including many types of fish—are similar to us in this aspect of their brain chemistry. And, thanks to the huge amount of prescription drugs that are flushed down the drain (American medical care facilities alone may flush as much as 250 million pounds of pharmaceuticals a year), these species are inadvertently being exposed to high concentrations of benzodiazepine in rivers, lakes, and streams.

In this week’s issue of Science, a group of researchers shows exposure to these drugs can cause significant behavioral changes in fish, changes that could potentially alter ecosystem dynamics.

Working in Sweden, the scientists found that treated wastewater had concentrations of oxazepam, a common benzodiazepine, of 0.73 µg per liter. The oxazepam concentration in a nearby stream where treated wastewater was released wasn’t much lower, at 0.58 µg per liter. Moreover, they found that European perch (Perca fluviatilis) that live in the water were actually accumulating the drug in their bodies; the oxazepam concentration in their tissue was more than six times that of the water.

To figure out whether drug exposure could be affecting the behavior of these fish, the researchers exposed perch to water with varying concentrations of oxazepam over seven days. The lowest experimental concentration was “environmentally-relevant,” representing conditions that perch likely experience in streams and rivers, while the highest concentration was more than 500 times higher.

Suspecting the drug could alter the behavior of the fish, the researchers quantified each perch in terms of several “personality” traits, both before and after benzodiazepine exposure. They examined three different tendencies—boldness, activity, and sociality—that are generally consistent within individuals and are often important to the animals’ fitness. Boldness was measured by testing how long it took each fish to explore a new environment; activity was quantified by the number of swimming bouts during the trial period; and sociality was a measure of how close the fish stayed to others.

Even small amounts of benzodiazepine affected the fishes' behavior. At the lowest concentration, oxazepam made the perch more active and less social; at higher levels of exposure, boldness increased as well.

As a better proxy for fitness-related behavior, the researchers looked at whether benzodiazepine exposure affected the feeding rate of the perch. Before exposure, it took a single fish more than 4½ minutes to consume 20 zooplankton. After low levels of exposure to oxazepam, the fish ate faster, shaving about 30 seconds off the pre-exposure time. Fish exposed to the highest level of oxazepam consumed the same amount of zooplankton in less than three minutes. Not only were the exposed fish feeding faster; they also started eating earlier in the trial than they had before being exposed to the drug.

These behavioral changes are likely to have significant effects on benzodiazepine-laced food webs, although it’s unclear exactly what the implications will be. The first possibility is that affected fish will feed so quickly that they will decimate the zooplankton population, causing a spike in algae (which zooplankton generally keep under control). Neither zooplankton nor algae have GABA receptors, so these species would only be affected indirectly by the presence of benzodiazepine in the water. Alternatively, overly-bold fish could bring on their own demise by taking unnecessary risks and leaving themselves open to predation.

The effects of pharmaceuticals on delicate food webs are unpredictable, but one thing is certain: whatever the consequences of benzodiazepine exposure will be, they will likely be irreversible if we can’t keep this drug out of the water.

27 Reader Comments

Wait... it's legal for an american medical care facility to FLUSH pharmaceuticals?

I work for a few pharmacists in Canada, and give my old drugs to them so that they can incinerate them. You should be able to bring any old drugs to a pharmacy to have them properly disposed of.. but I suppose that costs money, and isn't convenient.. and if it's not illegal, what do they care?

Wait... it's legal for an american medical care facility to FLUSH pharmaceuticals?

I work for a few pharmacists in Canada, and give my old drugs to them so that they can incinerate them. You should be able to bring any old drugs to a pharmacy to have them properly disposed of.. but I suppose that costs money, and isn't convenient.. and if it's not illegal, what do they care?

It is not. most of the flushed drugs actually come from individuals, and smaller clinics cutting corners and hoping not to get caught.

Wait... it's legal for an american medical care facility to FLUSH pharmaceuticals?

I work for a few pharmacists in Canada, and give my old drugs to them so that they can incinerate them. You should be able to bring any old drugs to a pharmacy to have them properly disposed of.. but I suppose that costs money, and isn't convenient.. and if it's not illegal, what do they care?

That's one vector. The other is just excess quantities being excreted in human urine.

We have similar disposal laws in some states in the US. Doesn't mean they're always followed.

Maybe the fish are blacking out and going on a binge? I have videos of myself after ingesting xanax and experiencing blackouts, in one of them it was New Years eve and I was in someones back yard in the desert in Arizona, yelling at the desert because I hated it so much. Then I went and gathered everyone in the house and forced them to smoke weed with me before I went on to raid the fridge like a hungry caveman. When I woke up the next day I had no recollection of any of it, all I remembered was nodding out over a game of Therapy. The videos revealed all though, and it was hilarious.

Wait... it's legal for an american medical care facility to FLUSH pharmaceuticals?

I work for a few pharmacists in Canada, and give my old drugs to them so that they can incinerate them. You should be able to bring any old drugs to a pharmacy to have them properly disposed of.. but I suppose that costs money, and isn't convenient.. and if it's not illegal, what do they care?

That's one vector. The other is just excess quantities being excreted in human urine.

We have similar disposal laws in some states in the US. Doesn't mean they're always followed.

For hospitals, it would mostly be via human waste. Actually, there are studies going back quite a ways looking at the levels of all manner of drugs in natural waters as a result of waste water treatment plants not really affecting these. That includes the classics like Prozac and contraceptives...

Benzos have all kinds of weird side effects. But as the doctors say: as long as the benefits overweigh the side effects we take them.

DCStone wrote:

Jiraiya wrote:

malejko wrote:

Wait... it's legal for an american medical care facility to FLUSH pharmaceuticals?

I work for a few pharmacists in Canada, and give my old drugs to them so that they can incinerate them. You should be able to bring any old drugs to a pharmacy to have them properly disposed of.. but I suppose that costs money, and isn't convenient.. and if it's not illegal, what do they care?

That's one vector. The other is just excess quantities being excreted in human urine.

We have similar disposal laws in some states in the US. Doesn't mean they're always followed.

For hospitals, it would mostly be via human waste. Actually, there are studies going back quite a ways looking at the levels of all manner of drugs in natural waters as a result of waste water treatment plants not really affecting these. That includes the classics like Prozac and contraceptives...

There are even warnings posted at US Pharmacies not to flush your meds but bring them over for disposal, but who really follows such rules?

In my environmental chemistry Ph.D. training I have been helping some local high school students measure other pharmaceuticals and personal care products (PPCPs) in the water of a local creek, river, and the effluent of a wastewater treatment plant. We mostly see caffeine (don't look for any benzodiazapines), but there isn't any long term chronic exposure data to say any of these drugs are safe for wildlife. There is quite a bit of research into new wastewater treatment plant designs that would remove more of these compounds before release, but they are all more expensive than current systems. Until we say we are willing to pay for more thorough treatment we will continue to expose wildlife to these drugs.As a side note, it has been extremely cool to see these students get so invested in this issue once they see how reliably we can measure a whole range of drugs in their water. If the methods were less expensive, it would be a great citizen science project.

Maybe the fish are blacking out and going on a binge? I have videos of myself after ingesting xanax and experiencing blackouts, in one of them it was New Years eve and I was in someones back yard in the desert in Arizona, yelling at the desert because I hated it so much. Then I went and gathered everyone in the house and forced them to smoke weed with me before I went on to raid the fridge like a hungry caveman. When I woke up the next day I had no recollection of any of it, all I remembered was nodding out over a game of Therapy. The videos revealed all though, and it was hilarious.

This is bad... Maybe it lacks thorough experimentation or testing. Good for you, you are able to cope up the problem.

It seems unlikely to help the fish in the long run. Proper feeding frequency is a heavily pressured trait in pretty much every species that does any active feeding (anything but autotrophs and stationary filter feeders, really). It seems unlikely that disturbing this would help a species, and even less likely that a spike in feeding frequency of heterotrophs would help an environment.

The concept of 250 million pounds of pharmaceuticals a year being flushed down the toilets in America is an interesting one. Of course Americans only represent about 4.5 % of the world's population.

Odd that benzodiazepines should illicit more boldness in fish. Oxazepam is normally prescribed for humans with anxiety disorders, sleep disorders or alcohol withdrawal problems. Benzodiazepines (tranquilizers) in general emulate barbiturates but they are supposed to impart less euphoria, suppress hallucinations and be less addictive.

Benzodiazepines have become some of the most prescribed (perhaps promiscuously) and abused drugs in the world. Many of these compounds are also associated with causing memory loss.

Trivia:- Chlordiazepoxide was the first benzodiazepine to be synthesized and marketed under the various trade names Klopoxid®, Librax®, Libritabs®, Librium®, Mesural®, Multum®, Novapam®, Risolid®, Silibrin®, Sonimen®, Tropium®, and Zetran®.

-Besides "Xanax" , alprazolam (C17H13ClN4) is marketed under 27 more brand names in the English speaking countries. Useful for anxiety or panic attacks and nausea caused by chemotherapy, it is short acting and said to be the most prescribed and misused benzodiazepine of all.

- According to Wikipedia: - Oxazepam is marketed in English speaking countries under the brand names Alepam, Medopam, Murelax, Noripam, Opamox, Ox-Pam, Purata, Serax and Serepax, as Vaben in Israel, and as Sobril and Oxascand in Sweden and as Sobril and Alopam in Norway and Zaxpam in India.

I would love to see a study like this in the US for the effects of alprazolam (Xanax). Oxazepam is hardly used at all in my region of the Pacific Northwest. Xanax on the other hand.... Regarding disposal, in my state the current recommendation is that prescription meds be made unpalatable (mix with coffee grounds or kitty litter) and sent to the landfill. The post human consumption waste stream could still be a significant source of environmentally active agents. To my knowledge, little or no long term study of consequences have ever been done. A host of PHd's in environmental studies await the enthusiastic.

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Kate Shaw Yoshida / Kate is a science writer for Ars Technica. She recently earned a dual Ph.D. in Zoology and Ecology, Evolutionary Biology and Behavior from Michigan State University, studying the social behavior of wild spotted hyenas.